Combining PrEP with contraception: a pilot test of an intervention to increase adherence to PrEP in adolescent girls and young women in Zimbabwe

将 PrEP 与避孕相结合：一项旨在提高津巴布韦少女和年轻女性对 PrEP 依从性的干预措施试点测试

• 批准号: 10693579
• 负责人: BARBARA A FRIEDLAND
• 金额: $ 11.95万
• 依托单位: POPULATION COUNCIL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-16 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10693579
• 关键词: AIDS prevention; Acceleration; Adherence; Africa South of the Sahara; Blood; Cause of Death; Client; Clinic; Clinical Research; Clinical Trials; Collaborations; Contraceptive Agents; Contraceptive Usage; Contraceptive methods; Cross-Over Studies; Development; Dryness; Enrollment; Epidemic; Ethinyl Estradiol/Levonorgestrel; Evaluation; Family; Feasibility Studies; Female; Female Adolescents; Focus Groups; Fumarates; Gelatin; HIV; Health Personnel; Incidence; Individual; Intervention; Interview; Manuals; Marketing; Menstrual cycle; Methods; Oral; Oral Contraceptives; Population; Pregnancy; Prevention; Prevention Research; Process; Provider; Questionnaires; Randomized; Recording of previous events; Regimen; Research; Spottings; Surveys; Tablets; Technology; Tenofovir; Testing; Training; Universities; Woman; Zimbabwe; aged; capsule; cost effective; emtricitabine; high risk; implementation science; older women; pill; pilot test; pre-exposure prophylaxis; preference; prevent; standard of care; truvada; unintended pregnancy; uptake; young woman

HIV is the leading cause of death in adolescent girls and young women (AGYW) aged 15-24 years. Despite advances in HIV treatment and prevention, AGYW remain at high risk, particularly in sub-Saharan Africa. Oral pre-exposure prophylaxis (PrEP) is highly effective and has the potential to make a dramatic impact on the HIV epidemic. Yet to date, most trials of PrEP in women have been unable to demonstrate efficacy, largely due to poor adherence among AGYW. Emerging evidence indicates that women may be more likely to use an HIV prevention method that also prevents pregnancy. We will test an intervention consisting of a single oral capsule providing both PrEP and contraception – a contraceptive multipurpose prevention technology (cMPT) – as a strategy for increasing PrEP adherence compared to oral PrEP alone. We will enroll AGYW who already use combined oral contraceptives (COCs) in Harare, Zimbabwe, where AGYW continue to be at high risk of HIV, more than half of contracepting women use COCs, and less than 1% of 15-35- year-old women are using PrEP. The cMPT intervention – a dual prevention pill (DPP) – will contain two marketed products: Truvada® [emtricitabine and tenofovir disoproxil fumarate (TDF)] and a COC [levonorgestrel (LNG)/ethinyl estradiol (EE)]. This research will implemented through a collaboration between the Population Council, which has global expertise in clinical trial, implementation science, feasibility studies and evaluation around female-initiated HIV prevention methods, and the University of Zimbabwe Clinical Trials Research Centre (UZ-CTRC), which has a long history of conducting HIV clinical studies and prevention research. In Aim 1, we will conduct qualitative formative research to explore the acceptability of combining Truvada with a COC to increase PrEP adherence through focus group discussions with AGYW and in-depth interviews (IDIs) with healthcare providers. In Aim 2, we will incorporate formative research findings into the development and pre-testing of 1) DPP packaging and client information materials; 2) adherence and acceptability questionnaires; and 3) a provider training manual. In Aim 3, we will compare the acceptability, preference, and adherence of the DPP intervention versus standard of care (2 separate pills: Truvada® and COC). In a 6-month randomized, crossover study, 30 AGYW (16-24 years old) in Harare, Zimbabwe will be assigned in random order to the sequence of the 2 regimens: the DPP or standard of care (2 separate pills). Each regimen will be used for 3 28-day menstrual cycles (approximately 3 months per regimen). At the end of 6 months, women will be asked to state their preference for the DPP or the 2 separate pills. We will assess and compare acceptability and adherence (via dried blood spots) of the 2 regimens, and socioecological factors (e.g., individual-, partner-, family-, clinic-level) associated with adherence and acceptability. We will explore facilitators and barriers to use through IDIs with 5 AGYW who complete the study and all AGYW who withdraw early. Acquiring confirmation now on the preference for a DPP from actual use with currently approved products will accelerate the availability of such a product in the marketplace. Given supportive findings in this project, we will outline a process for regulatory approval of the more cost-effective co- formulated pill.

艾滋病毒是15-24岁少女和青年妇女的主要死因。尽管取得了进展， 在艾滋病毒治疗和预防方面，AGYW仍然处于高风险之中，特别是在撒哈拉以南非洲。经口预暴露 PrEP是一种非常有效的预防措施，有可能对艾滋病毒流行产生巨大影响。但迄今为止， 大多数在女性中进行的PrEP试验都无法证明有效性，主要是由于AGYW的依从性差。 新出现的证据表明，妇女可能更有可能使用一种艾滋病毒预防方法， 怀孕我们将测试一种干预措施，包括一个单一的口服胶囊提供PrEP和避孕- a 避孕多用途预防技术（cMPT）-与口服相比，作为增加PrEP依从性的策略 单独使用PrEP。我们将在津巴布韦的哈拉雷招募已经使用复方口服避孕药（COCs）的AGYW， AGYW仍然处于艾滋病毒的高风险之中，一半以上的避孕妇女使用COCs，15-35岁的妇女中不到1%使用COCs。 cMPT干预-双重预防药丸（DPP）-将包含两种市售的 产品：Truvada® [恩曲他滨和富马酸替诺福韦酯（TDF）]和COC [左炔诺孕酮（LNG）/乙炔 雌二醇（EE）]。这项研究将通过与人口理事会之间的合作进行，该理事会拥有全球 在临床试验、实施科学、可行性研究和评估女性发起的艾滋病毒方面的专业知识 预防方法，以及津巴布韦大学临床试验研究中心（UZ-CTRC）， 进行艾滋病毒临床研究和预防研究的历史。在目标1中，我们将进行定性形成 通过焦点小组探讨Truvada与COC结合以增加PrEP依从性的可接受性的研究 与AGYW进行讨论，并与医疗保健提供者进行深入访谈。在目标2中，我们将 将形成性研究结果纳入1）DPP包装和客户信息材料的开发和预测试; 2） 依从性和可接受性问卷;以及3）供应商培训手册。在目标3中，我们将比较 DPP干预与标准治疗的可接受性、偏好和依从性（2种单独的药丸：Truvada®和 COC）。在一项为期6个月的随机、交叉研究中，津巴布韦哈拉雷的30名AGYW（16-24岁）将被分配到 2种方案的顺序随机排列：DPP或标准治疗（2片单独的药丸）。将使用每种方案 3个28天的月经周期（每个方案约3个月）。在6个月结束时，妇女将被要求 说明他们对DPP或2种单独药片的偏好。我们将评估和比较可接受性和依从性（通过 干血斑），以及社会生态因素（例如，个人、伙伴、家庭、诊所一级） 与依从性和可接受性相关。我们将与5名AGYW一起通过IDI探索促进因素和障碍 所有完成研究的人和所有提前退出的AGYW。现在就倾向于DPP获得确认 与当前批准的产品的实际使用相比，将加速这种产品在市场上的可用性。 鉴于该项目的支持性研究结果，我们将概述一个监管批准更具成本效益的联合治疗的过程， 配方药丸